England forward Billy Vunipola will be sidelined for three months after undergoing surgery on his broken left arm.
Vunipola was injured in Saracens' 13-3 Champions Cup victory over Glasgow on Sunday and will miss all of England's November internationals - including the Wallabies' visit to Twickenham on November 24.
The injury ruled him out of England's squad for their November internationals.
"Billy has fractured his left arm and will have surgery on Tuesday. He is expected to be out of action for around 12 weeks," Saracens said on their website.
Vunipola's brother prop Mako also suffered a calf strain while forward Isiekwe added to the national team's injury woes by suffering an ankle sprain.
The fitness of both players will be monitored.
The trio were part of England's training squad for the Autumn series against South Africa, New Zealand, Japan and Australia next month.
England have been unlucky with injuries, with lock Joe Launchbury ruled out after knee surgery last week while Bath fullback Anthony Watson and Exeter forward Sam Simmonds will also miss next month's games.
Eddie Jones names his squad for the November games on Thursday.
England plays South Africa, New Zealand, Japan and the Wallabies in the 2018 November Tests. Australia faces England on Saturday November 24 local, Sunday November 25 AEDT.
